Segment formation is one of the earliest stages in the development of higher animals. There is evidence in early Drosophila embryos that groups of cells ar committed into patterns that correspond to segments and that cell fates are transmitted to progeny cells. The mechanism by which cells are "determined" in this way is one of the central problems in understanding development. A key approach is to identify genes whose products are involved in the biological process of establishing this determination. We are concerned here with genes in D. melanogaster whose recessive loss-of-function mutations lead to "head 'n tail" segmentation defects. Specifically we have focused on the gene tailless as the outstanding representative of this class; we have shown that tailless mutants form fewer but larger posterior segments in the embryo and that head structures are altered. We expect that tailless+ is required for normal formation of the anterior and posterior-most ectodermal segments. Experiments are proposed to test the hypotheses that tailless acts early in development at specific locations and that the mutant alters the embryonic fate plan. Knowing the gene product will ultimately throw light on the nature of determination through the control of the number and locations of segments. In addition, by means of selecting mutations that interact with or suppress the tailless mutant, we will identify other genes that play a role in segment formation. Mutations will be sought at second sites where a loss-of-function makes tailless dominant, or where a dominant gain-of-function suppresses the tailless mutant phenotype. The genetic and developmental analysis of mutations and gene products coded at such second sites will corroborate their role in segment pattern formation. Selecting genes on the basis of their involvement with the tailless system in principle provides a powerful means of discovering all of the genes that are involved in a specific developmental step.